Cancer Genetics

Question 1

What does it mean for a tumor to be clonal?

Answer 1

They start as a single cell with a mutation and proliferates to form a group of similarly anormal cells. A tumor can usually be traced back to the original mutant

Question 2

When is a tumor malignant?

Answer 2

When the uncontrolled cell growth has a change in the normal organizational pattern of tissues or cells

Question 3

What technology can help determine clonality and follow disease progression?

Answer 3

karyotype

Question 4

During metastasis, do cells that invade change morphology?

Answer 4

No they keep original cell morphology

Question 5

How does cancer spread locally and systematically?

Answer 5

By invasion and metastasis respectively

Question 6

Name the type of cancer of mesenchymal tissue (bone, cartilage, muscle, fat)

Answer 6

Sarcoma

Question 7

Name the type of cancer of epitheliod tiussues

Answer 7

Carcinoma

Question 8

Name the type of cancer of hematiopoietic/lymphoid organs?

Answer 8

Leukemias

Question 9

What cells are affected in leukemias?

Answer 9

WBCs from bone marrow

Question 10

What cells are affected in lymphomas?

Answer 10

WBCs from the spleen and lymph nodes

Question 11

How do environmental mutages like UV light, asbestos, cig. Smoke, plastics , dyess (#3) cause cancer?

Answer 11

lead to changes in normal cell regulation and development

Question 12

What is an oncogene?

Answer 12

dominantly acting gene involved in unregulated cell growth and prolferation

Question 13

Give examples of viral oncogenes in humans

Answer 13

HPV (cervical cancer E6/E7), EBV (nasopharyngeal cancer, Hodgkin and Brukitt Lymphoma), HHV-8 (herpes virus-Kaposi sarcoma), HTLV (luekemia, HTLV-1 is Tcell)

Question 14

Growth factors, cell surface receptors, intracellular signal transduction, DNA binding protiens, are associated with what genes?

Answer 14

Proto-oncogenes - structurally important housekeeping genes involved in cell proliferation and development

Question 15

What activates a proto-oncogene and what is its effect?

Answer 15

A mutation (translocation, amplifacation, pt. mutation) that causes a change in gene regulation, transcription, or a ptn. Product generating alterations to cell growth, proliferation or differentiation

Question 16

Generally speaking, Gleevec targets what? Specifically?

Answer 16

A genetic lesion ; BCR-ABL tyrosine kinase

Question 17

What translocation is seen in Acute Promyelocytic Leukemia?

Answer 17

PML gene on 15 aand RARA gene on 17

Question 18

What kind of ptn. Prodcut is seen in APL?

Answer 18

CHIMERIC proteiin product

Question 19

What iS seen in FISH in APL?

Answer 19

1 RED, 1 GREEN, and 2 YELLOW (fusion signals)

Question 20

Loss or inactivation of what genetic element leads to neoplastic growth from altered phenotype?

Answer 20

Tumor Suppressors (examples: Gate keepers and caretakers)

Question 21

Is tumor suppressor induced cancer dominant or recessive?

Answer 21

recessive

Question 22

Gate keeper vs. caretaker, what’s the difference?

Answer 22

Gatekeeper regulates cell cycle or inhibits cell growth. Caretaker maintains cellular integrity by repairing DNA damage and therefore is needed for genetic stability

Question 23

3 important Tumor suppressors include _____ and are located on which chromosomes

Answer 23

RB1 -chormosome 13, P53of short arm of chromosome 17, MTS1 (multiple tumor suppressor1)

Question 24

How do tumor suppressor mutations often manifest themselves? What diagnostic tech. can be helpful?

Answer 24

Solid Tumor; karyotype analysis

Question 25

A mutation at at band 13q14.2, leads to what disease?

Answer 25

Retinoblastoma in neonates to children up to 5 years

Question 26

Retinoblastoma treatments include

Answer 26

laser surgery, enucleation

Question 27

Sporadic and inherited retinoblastoma leads to what phenotype?

Answer 27

unilateral or bilateral respectively tumor od the immature retinal cells of the eye (retinoblasts)- 2 mutations are ncessary to knock out the function of a specific RB1 locus (aka Knudson's 2-Hit Hypothesis)

Question 28

A specific tissue target is asscoiated with what tumor suppressor mutation?

Answer 28

Primary mutation

Question 29

2 primary genes asscoiated with breast cancer include _____ and are located on which chromosomes

Answer 29

BRCA1 (chromosome 17, near NF1 and p53) and BRCA2 (chromosome 13 near RB1)

Question 30

What testing should be done for Familial breast cancer?

Answer 30

Review of Pedigrees to assess risk followed dby testing for BRCA1 and BRCA2 (though this is complicated by the presence of multiple mutations)

Question 31

What population is at risk for familial breast cancer?

Answer 31

Ashkenazi Jewish

Question 32

What diseases are associated with Chromosome Breakage Syndromes?

Answer 32

Fanconi Anemia, Bloom Syndrome, Ataxia Telangiectasia, Xeroderma Pigmetosum, cockayne Syndrome

Question 33

Breast cancer, Hereditary Non-polyposis Colon Cancer, and bladder cancer are associated with what kind of mutation?

Answer 33

Caretaker mutation

Question 34

What are two possible effects of errors in sister chromatid exchange?

Answer 34

Triradials- instead of the normal linear chromosome, a replication error has resulted in a Y-shaped, forked structure or also excessive breakage can lead to chromosome deletiona dn genomic defects

Question 35

Which disease is associated with mutations in DNA ligase 1 or DNA helicase?

Answer 35

Bloom syndrome-15q26.1

Question 36

Which disease is associated with mutations in Excision repair cross complementation?

Answer 36

Cockayne Syndrome, 5q121, 10q11

Question 37

Which disease is associated with mutations in Excision repair?

Answer 37

Xeroderma Pigmentosum- 3p25, 13q33, chr.9

Question 38

What results from a defect in mismatch repair?

Answer 38

2 cell lines that can proliferate, resulting in a new, potentiallyabnormal, cell line

Question 39

What technology can be used to determine DNA repair defects? In what field is this useful?

Answer 39

Microsatellite Analysis; investigative- for DNA fingerprinting

Question 40

Hereditary Nonpolypsis Colon Cancer is predominantly caused by which 2 genes?

Answer 40

MSH2 and MLH1 mismatch repair genes

Question 41

What technology should be studied to determine the majority of HNPCC?

Answer 41

Microsatellites because they are sensitive to effects in DNA repair because they are subject to replication error due to slippage

Question 42

What can be used to monitor the presence and evolution of clones?

Answer 42

karyotype

Question 43

What describes the change over time in the karyotype due to acquisition of different mutations?

Answer 43

Karyotype evolution

Question 44

What are constitutional findings?

Answer 44

original DNA and chromosome complement that is the foundation for the genetic constitution in all cells of the body; originating in the zygote

Question 45

What describes a change that occurs in the DNA or constitutional karyotype and is usually present in a single cell line?

Answer 45

an acquired anomaly

Question 46

examples of loss of genetic material

Answer 46

deletion ; monosomy

Question 47

examples of gain of genetic material

Answer 47

duplication, trisomy, gene amplification

Question 48

relocation of genetic material

Answer 48

translocation

Question 49

t (8;21) (q22;q22) translocation, inv (16)(p13q22) and t (4;11) translocation is associateed with what diseases?

Answer 49

Leukemia: AML-M2, AML-M4, ALL respectively

Question 50

What is Loss of Heterozygosity? How does it appear?

Answer 50

Apparent homozygosity or hemizygosity in a tissue which demonstraets heterozygosity constitutionally; on a karyotype it can appear as one single band despite having multiple copies of a choromosome (Therefore, LOH does not mean ther is only a single allele present)

Question 51

Which chromosome is affected in PML?

Answer 51

15

Question 52

Which chromosome is affected in Retinoic acid receptor alpha?

Answer 52

17

Question 53

What Is a mixed sex transplant?

Answer 53

male donor : female recipient or reverse

Question 54

What technology helps determine the relative proportions of the populations in a mixed sex transplant?

Answer 54

FISH: test for 2 Xs or X+Y and tabulate

Question 55

Which drug will induce a response in patients with beast cancer with gene amplification?

Answer 55

Herceptin

Question 56

Whcich cancer is HER-2/neu gene amplification associated with?

Answer 56

breast cancer

Question 57

Describe a normal cell and tumor cell HER2 signals on FISH assay

Answer 57

2 green control signals and 2 HER2 signals in a normal cell. 2 green control signals per cell but multiple red signals indicate gene amplification in a tumor cell.

Question 58

Which technologies detect BCR-ABL arrangements? Relative frequency of use for detection?

Answer 58

95% karyotype + FISH, 5% PCR

Question 59

Which genetic study allows us to determine relatedness between different diseases (ex.disease course/clinical manifestation)?

Answer 59

Expression Arrays

Question 60

You want to discriminate bet. Normal prostate tissue and tuissue with prostate cancer, what type of microarray analysis will provide valuable information on genes and proteins specific to each?

Answer 60

Expression Arrays

Question 61

What kind of mutation is usually required for cancerdisease expression?

Answer 61

Somatic . Disease is due to multi-step process at somatic cell level

Question 62

Carrrier parent of an inherited cancer has what percentage chance of passing on a mutation?

Answer 62

50%

Question 63

What is Li Fraumeni?

Answer 63

A type of familial cancer associated with the inheritance of a mutation of p53 causing loss of checkpoint control of DNA damage. It has no specific target tissue.

Question 64

What is TGFBR2?

Answer 64

A growth factor receptor. It is associated with rarer cases of HNPCC.